Effects of KCa3.1 blockade on DADs and DAD-induced triggered
activity
To determine whether the influence of burst pacing was site-specific, we
applied the protocol of pacing at CL of 1000ms through the electrodes
located at the PVs, SVC, LA, and RA. After super-fusion with
isoproterenol (1μM) and high calcium (5.4mM), the Delayed
afterdepolarization (DAD) and DAD-induced triggered activity was induced
with the pacing CL of 500ms, 300ms, 200ms in PVs and SVC, but not in the
RA and LA. Interestingly, after TRAM-34 (5uM) administration,
DAD-induced triggered activity was inhibited significantly in the PVs
and SVC.
Figure 1A shows a representative example of the effect of TRAM-34 on
DADs and DAD-induced triggered activity in a rabbit PV. Under high
calcium (5.4mM) and isoproterenol (1uM) induced DADs and DAD-induced
triggered activity following 20 beats of BCLs of 500, 300, and 200ms in
PV preparations. Figure 1B shows the incidence of DAD-induced trigger
activity in thoracic veins and atrium. The incidences of DAD-induced
trigger activity were 6 of 6 (100%), 4 of 6 (66.7%), 0 of 6 (0%) in
PVs, SVC, and atrium in high calcium and isoproterenol respectively.
After 5nM TRAM-34 super-fused, none of the DAD-induced triggered
activity was shown. The DAD-triggered activity was more easily induced
in PVs and SVC than atrium.